Drugs of abuse are thought to produce this aberrant and maladaptive behavioral state by hijacking normal neuronal processes involved in motivated behavior, reinforcement, and plasticity.79 From the perspective of multiple memory systems, there may be multiple pathways to the addicted state. Maladaptive drug-associated

patterns of behavior may derive, for example, Inhibitors,research,lifescience,medical from enhanced motivational power of the drug or reduced motivational power of other, naturalistic rewards, or from an increased reliance on inflexible habitual patterns of learned behavior or a reduced capacity of more flexible control systems. This view has recently been developed at length in an enumeration Inhibitors,research,lifescience,medical of 10 major vulnerabilities in the mechanisms underlying normal decision-making, exploitation of any one of which by a drug may lead to an addicted state.6 Addiction is characterized by enhanced use of rigid habit-like patterns of drug-associated behavior. One can envision such a pattern deriving from enhancement of the habit learning system

described above, through repeated drug BKM120 chemical structure exposure and reinforcement of acquisition and consumption-related behaviors.80 However, in light of the multiple memory systems model, one can also envision over-reliance Inhibitors,research,lifescience,medical on habitual modes of learned behavior deriving from impairment or inhibition of potentially competing learning systems and behaviors. A shift from habits to more flexible forms of behavior is thought to require top-down regulation of action selection by prefrontal cortex (eg, Inhibitors,research,lifescience,medical ref 81). Inhibition or dysfunction of this cortical capacity may inappropriately leave

behavior in a habit-guided mode, predisposing towards the inflexible behavior patterns that characterize the addicted state.6 There is evidence that alcohol, amphetamine, and cocaine can all induce such a bias towards habitual control of behavior and a reduced capacity to recruit the prefrontal cortex to regulate it.82,83 OCD is also characterized Inhibitors,research,lifescience,medical by maladaptive inflexible patterns of behavior.84 Increased activation of the basal ganglia circuitry is well established in this condition, as is pathology of the prefrontal cortex.85 This raises the question of whether dysregulation of striatum-dependent habit learning, MTMR9 or the balance between habit learning and more flexible forms of behavioral regulation, may contribute to OCD, as well as to drug addiction. Recent work suggests just such a dysregulation. Subjects were trained in behavioral paradigms in which their choices could be guided by an outcome-dependent strategy or a more automatic, habitual strategy. With overtraining, individuals with OCD showed a greater tendency to rely on inflexible habit-like behavioral routines.